Nifedipine Tocolytic Lilia 12jan2005

7/30/2019 Nifedipine Tocolytic Lilia 12jan2005

1/3

Review of efficacy & safety of nifedipine as tocolyt ic in late pregnancy.

Definition

Preterm birth is the birth occurring between 20 and 36 weeks of gestation. It is a majorcontributor to perinatal mortality and morbidity, and affects 6-7% of births in developed

countries1.

Currently there is 1 item for tocolysis on the WHO EML, Section 22. Oxytocics andantioxytocics:

22.2 Antioxytocics salbutamol, tablet, 4 mg (as sulfate) and injection, 50 g (as sulfate) in 5-ml

ampoulewith the footnote stating: The public health relevance and/or efficacy and/or safety ofthis item has been questioned and its continued inclusion in the Model List will bereviewed at the next meeting of the Expert Committee.

Nifedipine is listed on the WHO EML, Section 12. Cardiovascular medicines:12.3 Antihypertensive medicines

nifedipine, sustained-release formulations tablet 10 mg

Nifedipine is listed on the Anatomical Therapeutic Chemical (ATC) classification indexwith Defined Daily Doses (DDDs) (WHO Collaborating Centre for Drug StatisticsMethodology), Oslo, Norway, 2004 under section C08 Calcium channel blockers C08C A05 Nifedipine.

The application for listing of Nifedipine, regular tablets or capsules 10mg and 20mg, as tocolytic is supported by strong clinical evidence of its superiority tobetamimetics and magnesium sulfate in acute tocolysis inhibiting preterm labour. Theeffects of nifedipine in suppression of preterm labour were critically assessed andsummarised in a meta-analysis2 and a Cochrane Systematic Review3.

Meta-analysis of nifedipine versus ritodrine for suppression of preterm labourconcluded that nifedipine should be the drug of choice for the suppression of pre-termlabour (positive commentary of the NHS Centre for Reviews and Dissemination (CRD)of the Cochrane collaboration for the published pooled analysis)

4.

Nifedipine was studied in ten out of twelve randomised controlled trials includedin the Cochrane Review involving totally 1029 women. Nifedipine was compared withbetamimetics (ritodrine and terbutaline (1 trial)) and magnesium sulfate (1 trial).Nicardipine was another calcium channel blocker assessed in this review.

Efficacy of tocolysis.The advantage in efficacy of nifedipine (calcium channel blockers) vs betamimetics ormagnesium sulfate was characterised by:

reduction of the number of women giving birth within seven days of receivingtreatment (relative risk (RR) 0.76 with 95% Confidence interval (CI) 0.60 to 0.97)l;

reduction of the number of women giving birth prior to 34 weeks of gestation (RR

0.83; 95% CI 0.69 to 0.99).


2/3

Efficacy in terms of neonatal outcomes.

Nifedipine (calcium channel blockers) demonstrated the major advantage overtraditionally used tocolytics (betamimetics and magnesium sulfate) in its favourableeffects on neonatal outcomes characterised by reduction of the frequency of:

neonatal respiratory distress syndrome (RR 0.63; 95% CI 0.46 to 0.88),

necrotising enterocolitis (RR 0.21; 95% CI 0.05 to 0.96),

intraventricular haemorrhage (RR 0.59 95% CI 0.36 to 0.98)

and neonatal jaundice (RR 0.73; 95% CI 0.57 to 0.93).

Maternal side effects.Nifedipine (calcium channel blockers) proved much better overall safety profilecompared with betamimetics and magnesium sulfate, documented by reduction in therequirement for women to have treatment ceased due to adverse drug reaction (RR

0.14; 95% CI 0.05 to 0.36),

Later clinical trial confirmed the conclusion about superiority of nifedipine inefficacy and safety in inhibiting preterm labour

5,6.

Maintenance therapy in tocolysis.Benefits and harms of maintenance therapy for preventing preterm birth afterthreatened preterm labour with calcium channel blockers as well as with other tocolyticsremain unclear

7,8,9,10

,11

and further research is warranted (Cochrane SystematicReview

12based on the results of 1 trial

13).

ConclusionHigh quality clinical evidence has accumulated to form a convincing argument to list

nifedipine as an antioxytocic (tocolytic) for inhibiting preterm labour, tablets, capsules,10 milligrams; 20 milligrams on the WHO Model List of Essential Medicines.

The following additions are suggested to the text for the WHO Model Formulary:

Tablets , nifedipine 10 mg, 20 mg (for acute tocolysis)

Capsules , nifedipine 10 mg, 20 mg (for acute tocolysis)

In Uses: uncomplicated premature labour between 20-33 weeks of gestation as acutetocolysis.In Dose (based on the largest trial with the most favourable outcomes)

14: Premature

labour for acute tocolysis, ADULT initially sublingually , 10 milligrams, repeated every20 minutes to maximum dose of 40mg in the first hour. Once contractions ceased 20milligrams every 4 hours for 48 hours, then maintenance (orally) 10 milligrams every 8hours until 34 weeks of gestation.

Professor Lilia Ziganshina,

WHO Expert Committee Member, Kazan, Russian Federation9 January 2005


3/3

1

King JF, Flenady VJ, Papatsonis DNM, Dekker GA, Carbonne B. Calcium channel blockers for inhibitingpreterm labour (Cochrane Review). In: The Cochrane Library, Issue 3, 2004. Chichester, UK: John Wiley& Sons, Ltd.

2Oei S G, Mol B W, de Kleine M J, Brolmann H A. Nifedipine versus ritodrine for suppression of preterm

labor: a meta-analysis.Acta Obstetricia et Gynecologica Scandinavica. 1999. 78(9). 783-788.

3King JF, Flenady VJ, Papatsonis DNM, Dekker GA, Carbonne B. Calcium channel blockers for inhibiting

preterm labour (Cochrane Review). In: The Cochrane Library, Issue 3, 2004. Chichester, UK: John Wiley& Sons, Ltd.

4NHS Centre for Reviews and Dissemination. Nifedipine versus ritodrine for suppression of preterm

labor: a meta-analysis (Structured abstract) CRD database number: DARE-992135 In: The CochraneLibrary, Issue 3, 2004. Chichester, UK: John Wiley & Sons, Ltd

5Papatsonis DN, van Geijn HP, Bleker OP, Ader HJ, Dekker GA Hemodynamic and metabolic effects

after nifedipine and ritodrine tocolysis. International Journal of Gynaecology & Obstetrics 2003 Jul, 1: 5-10.

6

Zhang X, Liu M[Clinical observations on the prevention and treatment of premature labor withnifedipine]. [Chinese]. Hua-Hsi i Ko Ta Hsueh Hsueh Pao [Journal of West China University of MedicalSciences], 2002; 33, 2: 288-90.

7Berkman ND, Thorp JM, Lohr KN, Carey TS, Hartmann KE, Gavin NI et al. Tocolytic treatment for the

management of preterm labor: a review of the evidence. American Journal of Obstetrics andGynecology 2003;188(6):1648-59.

8Meirowitz NB, Ananth CV, Smulian JC, Vintzilous AM. Value of maintenance therapy with oral tocolytics:

a systematic review. Journal of Maternal-Fetal Medicine 1999;8:177-83.

9Sanchez-Ramos L, Kaunitz AM, Gaudier FL, Delke I. Efficacy of maintenance therapy after acute

tocolysis: a meta-analysis. American Journal of Obstetrics and Gynecology 1999;181:484-90.

10Crowther CA, Hiller JE, Doyle LW. Magnesium sulphate for preventing preterm birth in

threatened preterm labour (Cochrane Review). In: The Cochrane Library, Issue 3, 2004.Chichester, UK: John Wiley & Sons, Ltd.

11Nanda K, Cook LA, Gallo MF, Grimes DA. Terbutaline pump maintenance therapy after threatened

preterm labor for preventing preterm birth (Cochrane Review). In: The Cochrane Library, Issue 3, 2004.Chichester, UK: John Wiley & Sons, Ltd.

12Gaunekar NN, Crowther CA. Maintenance therapy with calcium channel blockers for preventing

preterm birth after threatened preterm labour (Cochrane Review). In: The Cochrane Library, Issue 3,2004. Chichester, UK: John Wiley & Sons, Ltd.

13 Carr DB, Clark AL, Kernek K, Spinnato JA. Maintenance oral nifedipine for preterm labor: a randomizedclinical trial. American Journal of Obstetrics and Gynecology 1999;181:822-7.

14Papatsonis DN, van Geijn HP, Ader HJ, Lange FM, Bleker OP, Dekker GA. Nifedipine and

ritodrine in the management of preterm labor: a randomized multicenter trial. Obstetrics andGynecology 1997;90(2):230-4.

Documents

Nifedipine Tocolytic Lilia 12jan2005